Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cancer genetics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed2002

Complexities of cancer research: mouse genetic models.

Cancer susceptibility is a complex interaction of an individual's genetic composition and environmental exposures. Huge strides have been made in understanding cancer over the past 100 yr, from recognition of cancer as a genetic disease, to identification of specific carcinogens, isolation of oncogenes, and recognition of tumor suppressors. A tremendous amount of knowledge has accumulated about the etiology of cancer. Cancer genetics has played a significant role in these discoveries. Analysis of high-risk familial cancers has led to the discovery of new tumor suppressor genes and important cancer pathways. These families, however, represent only a small fraction of cancer in the general population. Most cancer is instead probably the result of an intricate interaction of polymorphic susceptibility genes with the sea of environmental exposures that humans experience. Although the central cadre of cancer genes is known, little is understood about the peripheral genes that likely comprise the polymorphic susceptibility loci. The challenge for cancer genetics is therefore to move forward from the mendelian genetics of the rare familial cancer syndromes into the field of quantitative trait loci, susceptibility factors, and modifier genes. By identifying the genes that modulate an individual's susceptibility to cancer after an environmental exposure, researchers will be able to gain important insights into human biology, cancer prevention, and cancer treatment. This article summarizes the current state of quantitative trait genetic analysis and the tools, both proven and theoretical, that may be used to unravel one of the great challenges in cancer genetics.

Animals↗
PubMed2005

Gastric cancer: new genetic developments.

Gastric cancer's (GC) incidence shows large geographic differences worldwide with the lowest rates occurring in most Western industrialized countries including the United States and the United Kingdom; in contrast, relatively high rates of GC occur in Japan, Korea, China, and South America, particularly Chile. The Laurén classification system classifies GC under two major histopathological variants: 1) an intestinal type and 2) a diffuse type. The intestinal type is more common in the general population, more likely to be sporadic and related to environmental factors such as diet, particularly salted fish and meat as well as smoked foods, cigarette smoking, and alcohol use. It exhibits components of glandular, solid, or intestinal architecture, as well as tubular structures. On the other hand, the diffuse type is more likely to have a primary genetic etiology, a subset of which, known as hereditary diffuse gastric cancer (HDGC), is due to the E-cadherin (CDH1) germline mutation. The diffuse type pathology is characterized by poorly cohesive clusters of cells which infiltrate the gastric wall, leading to its widespread thickening and rigidity of the gastric wall, known as linitis plastica. Helicobacter pylori infection is associated with risk for both the intestinal and diffuse varieties of gastric cancer. Germline truncating mutations of the CDH1 gene, which codes for the E-cadherin protein, were initially identified in three Maori families from New Zealand that were predisposed to diffuse GC. Since then, similar mutations have been described in more than 40 additional HDGC families of diverse ethnic backgrounds. It is noteworthy that two-thirds of HDGC families reported to date have proved negative for the CDH1 germline mutation. A number of candidate genes have been identified through analysis of the molecular biology of E-cadherin. Patients with evidence of the CDH1 germline mutation in the context of a family history of HDGC must be considered as candidates for prophylactic gastrectomy, given the extreme difficulty in its early diagnosis and its exceedingly poor prognosis when there is regional or distant spread. Specifically, the E-cadherin cytoplasmic tail interacts with catenins, assembling the cell-adhesion complex involved with E-cadherin mediated cell:cell adhesion. Beta-catenin and gamma-catenin compete for the same binding site on the E-cadherin cytoplasmic tail, directly linking the adhesion complex to the cytoskeleton through alpha-catenin. Beta-catenin gene (CTNNB1) mutations have been described predominantly in intestinal-type gastric cancers and CTNNB1 gene amplification and overexpression have recently been described in a mixed-type gastric cancer. This paper reviews the genetics of both intestinal and diffuse types of gastric carcinoma, their differential diagnosis, molecular genetics, pathology, and, when known, their mode of genetic transmission within families.

Adenocarcinoma↗
PubMed1999

The Cancer Genome Anatomy Project: EST sequencing and the genetics of cancer progression.

As the process of tumor progression proceeds from the normal cellular state to a preneoplastic condition and finally to the fully invasive form, the molecular characteristics of the cell change as well. These characteristics can be considered a molecular fingerprint of the cell at each stage of progression and, analogous to fingerprinting a criminal, can be used as markers of the progression process. Based on this premise, the Cancer Genome Anatomy Project was initiated with the broad goal of determining the comprehensive molecular characterization of normal, premalignant, and malignant tumor cells, thus making a reality the identification of all major cellular mechanisms leading to tumor initiation and progression ([Strausberg, R.L., Dahl, C.A., and Klausner, R.D. (1997). "New opportunities for uncovering the molecular basis of cancer." Nat. Genet., 16: 415-516.], www.ncbi.nlm.nih.gov/ncicgap/). The expectation of determining the genetic fingerprints of cancer progression will allow for 1) correlation of disease progression with therapeutic outcome; 2) improved evaluation of disease treatment; 3) stimulation of novel approaches to prevention, detection, and therapy; and 4) enhanced diagnostic tools for clinical applications. Whereas acquiring the comprehensive molecular analysis of cancer progression may take years, results from initial, short-term goals are currently being realized and are proving very fruitful.

Databases, Factual↗
PubMedDate not supplied

Gene therapy in cancer.

Genetics have and will continue to have a strong and often controversial impact on our lives. Since the first human gene therapy in 1989, data from some 400 officially approved trials have been reported; only a handful appears promising. Of course, one must discern between gene replacements that correct inherited genetic disorders for life and the specific replacement of mutant genes that initiate or maintain the malignant phenotype with a correct gene copy. A truly reliable, safe, and efficient gene delivery system is not yet available, and many techniques have serious limitations or may be outright dangerous. Nevertheless, strong scientific and economic forces keep driving genetic research in cancer, with the promise of immortal fame (and even greater monetary rewards).

Drug Delivery Systems↗
PubMed1995

Familial pancreatic cancer and the genetics of pancreatic cancer.

In our current understanding of pancreatic carcinoma, these neoplasms can arise either sporadically or in familial clusters. Extensive chromosome abnormalities are frequent, as is loss of heterozygosity at loci known to contain the tumor suppressor genes DCC, p53, and MTS1. Although the genetic examination of all pancreatic cancers is important, the examination of familial cases is especially useful in that these allow the identification of uniform genetic alterations that are inherited through the germ line. Much additional work needs to be done before the genetic basis of pancreatic cancer is completely understood. Although our knowledge is limited, it is clear that genetic analyses can be used to establish the prognosis for a patient with pancreatic cancer and, it is hoped, will someday be used in the management, treatment, and detection of pancreatic cancer.

Adenocarcinoma↗
PubMed2004

CCL2 (monocyte chemoattractant protein-1) and cancer.

Genetic analyses of cancer in humans indicate that chemokines and their receptors are unlikely to play direct roles in pathogenesis. However, these molecules have pleiotropic effects that impact on cancer pathobiology in animal models, and there is evidence that they may do the same in humans. Given their protean properties, chemokines could have tumor-promoting, tumor-suppressing activities, or either depending on context. An example is found in CCL2, a chemokine that attracts and activates mononuclear cells. In some settings, it stimulates host anti-tumor activities. However, tumor cells themselves secrete CCL2 suggesting that it has growth promoting effects. These have been documented in animal models and clinical epidemiological studies. If CCL2's protumorigenic activities can be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer.

Chemokine CCL2↗
PubMed2006

[Origin and role of aneuploidy in cancer].

Genetic aberrations of cancer cells have a profound impact for prognosis in several malignant neoplasias. The understanding of their origin is the basis for the development of new therapeutic options. Aneuploidy is observed in a large variety of premalignancies and tumors. Aneuploid cells harbor less or more than 46 chromosomes. The exact role of aneuploidy in tumorigenesis is still not clear. It has long been debated, whether aneuploidy directly contributes to tumorigenesis or reflects nonspecific changes during tumor progression. Several mechanisms are thought to be responsible for the generation of aneuploid sets of chromosomes: these comprise failure in cell division, such as defective chromosome separation caused by compromised mitotic checkpoint signaling or centrosome aberrations. Moreover, telomere shortening and defective DNA-damage signaling appear to be powerful driving forces of genomic instability. The loss of telomere sequences at the end of each chromosome and DNA double-strand breakage accompanied by compromised damage signaling favor fusion of chromosomes and generation of aneuploidy. Furthermore, aneuploidy arises to a much higher degree from a tetraploid state when compared to diploid cells. The frequent observation of the described defects in pre- and malignant cells supports the hypothesis that aneuploidy contributes to tumorigenesis.

Aneuploidy↗
PubMed2006

Regional copy number-independent deregulation of transcription in cancer.

Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.

Cell Line, Tumor↗
PubMedDate not supplied

Identification of metastasis-associated genes in prostate cancer by genetic profiling of human prostate cancer cell lines.

OBJECTIVES: Prostate cancer (PCa) is a heterogeneous tumour entity with known interindividual differences in biological behaviour regarding tumour aggressiveness and metastatic potentiaL To date, the prediction of the metastatic status of patients with PCa has not been possible. To identify the molecular causes behind these differences, the gene expression profiles of two cell lines (LNCaP and LNCaP C4-2) with different metastatic potentials were examined using DNA microarray technology. MATERIALS AND METHODS: LNCaP and LNCaP C4-2 cells were cultured under standard conditions. RNA was isolated using Trizol extraction. After processing the total RNA according to the manufacturer's instructions, we performed Affymetrix GeneChip analysis with HG-U133A chips. Data analysis was performed using NetAffx, dChip, GenMAPP and OMIM software. RESULTS: After statistical evaluation of the raw data, we obtained a set of 158 differently expressed probe sets in the LNCaP and LNCaP C4-2 cells. The search for genes associated with proliferation, cell metabolism, growth factors, metastatic potential and tumour progression in this list revealed a number of 42 differently expressed probe sets. The comparison of this list of probe sets with the literature resulted in a list of 14 differently expressed genes which could well contribute to the metastatic potential and progression of PCa. Of these 14 genes only 6 (Cip1, IGF-1, NK4, CXCL 12, ILGF2R, RHOE) have already been associated with PCa, whereas the other 8 genes (FSTL-1, SOCS-2, Midkine, Thrombospondin 1, Secretory leukocyte protease inhibitor, Desmoglein 2, MLT 1, PTPRF) had not been previously related to PCa. CONCLUSION: DNA microarray technology offers the possibility of screening a large number of genes with regard to alterations in the expression level or mutations. In this study, we identified 14 genes that are most probably associated with the higher metastatic potential of LNCaP C4-2 cells as compared to LNCaP cells. Eight of these 14 genes are potential new molecular markers for assessing the metastatic potential of PCa, or may serve as therapeutical targets.

Apoptosis↗
PubMed1993

Genetic mapping of a locus predisposing to human colorectal cancer.

Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease.

Chromosome Mapping↗
PubMed2005

Immortalizing the complexity of cancer metastasis: genetic features of lethal metastatic pancreatic cancer obtained from rapid autopsy.

The virtual lack of well-characterized metastatic pancreatic cancer tissues for study has limited systematic studies of the metastatic process of this deadly disease. To address this important issue, we have instituted a rapid autopsy protocol for the collection of high quality tissues from patients with metastatic pancreatic cancer, called the Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP). At the time of preparation of this manuscript, 20 patients with metastatic pancreatic cancer and one patient with metastatic colon cancer have undergone a rapid autopsy in association with the GICRMDP. The average time interval achieved for these 21 patients was 8.0 hours, with more than 500 individual samples of matched high quality primary and metastatic pancreatic cancer tissues, peritoneal/pleural fluid and blood obtained so far. For the first four patients in which the autopsy was performed in <6 hours, we have successfully xenografted the primary tumor and/or two to four independent matched metastases from a variety of target organ sites, with a take rate of almost 60% for the first 26 xenografted tumors attempted. In an initial survey of KRAS2, TP53 and DPC4 genetic status in lethal metastatic pancreatic cancers, activating KRAS2 mutations were detected in 82% of cases and inactivating TP53 mutations in 55% of cases, consistent with rates of genetic alteration of these genes in early stage pancreatic cancers. However, DPC4 inactivation was found in 75% of patients analyzed, suggesting that genetic inactivation of the DPC4 tumor suppressor gene continues to be selected for with growth at the primary site and metastatic spread to other organs. The invaluable tissue resources generated by the success of the GICRMDP will provide an unparalleled resource for study of metastatic pancreatic cancer and of the metastatic process in general.

Adenocarcinoma↗
PubMed2005

Chromosomal instability and human cancer.

Genetic instability is a defining feature of human cancer. The main type of genetic instability, chromosomal instability (CIN), enhances the rate of gross chromosomal changes during cell division. CIN is brought about by mutations of CIN genes, i.e. genes that are involved in maintaining the genomic integrity of the cell. A major question in cancer genetics is whether genetic instability is a cause and hence a driving force of tumorigenesis. A mathematical framework for studying the somatic evolution of cancer sheds light onto the causal relations between CIN and human cancer.

Chromosomal Instability↗
PubMed2005

Genetic counseling outcomes: perceived risk and distress after counseling for hereditary colorectal cancer.

Genetic counseling may turn risk information into cancer prevention behavior by modifying health beliefs and cancer-related distress. We assessed the effect of genetic counseling on these factors in 101 adult first-degree-relatives of colorectal cancer patients from families with known or suspected hereditary nonpolyposis colorectal cancer. Before counseling and once afterward, subjects completed self-report measures of perceived lifetime risk and cancer-distress. Most persons overestimated their cancer risk, and higher perceived risk was associated with believing that colorectal cancer cannot be prevented. Individual perceived risk changed after counseling, although mean perceived risk was unchanged. After adjusting for baseline risk, older persons and those with higher estimated objective cancer risk had larger postcounseling decreases. Distress after counseling was positively correlated with baseline distress and anxiety symptoms, and inversely correlated with tolerance for ambiguity. The findings suggest counseling interventions that should increase the likelihood of screening and offer hypotheses for future research.

Adaptation, Psychological↗
PubMed2003

US physicians' attitudes toward genetic testing for cancer susceptibility.

Genetic testing for an inherited susceptibility to cancer is an emerging technology in medical practice. Little information is currently available about physicians' attitudes toward these tests. To assess US physicians' opinions on unresolved issues surrounding genetic testing, a 15-min survey was administered to a stratified random sample of 1,251 physicians from 8 specialties, selected from a file of all licensed physicians in the US (response rate = 71.0%). Dependent measures included physicians' attitudes toward genetic counseling and testing qualifications, availability of guidelines, patient confidentiality and insurance discrimination issues, and clinical utility of genetic tests. More than 89% of physicians reported a need for physician guidelines, 81% thought that patients with positive genetic test results are at risk for insurance discrimination, and more than 53% thought that it was difficult to ensure the confidentiality of test results. Almost 25% indicated that genetic tests for cancer susceptibility have too many inaccurate or ambiguous results; nearly 75% thought that clear guidelines are not available for managing patients with positive test results. Only 29% of physicians reported feeling qualified to provide genetic counseling to their patients. More than 84% of oncologists considered themselves qualified to recommend genetic testing to their patients compared with 40% of primary care physicians (PCPs), and 57% of tertiary care physicians (TCPs). US physicians expressed great uncertainty about issues surrounding genetic testing for cancer susceptibility. Results of this national survey underscore the need to provide physicians with clear guidelines on the use of genetic cancer susceptibility tests and effective medical training on their appropriate implementation.

Attitude of Health Personnel↗
PubMed1998

Rectal cancer--from genetics to the therapy.

Cancer of the colon and rectum is major cause of cancer-associated morbidity and mortality. Globally, it is the third most common cancer in males and fourth most common in females. Colorectal cancer is primarily a genetic disease with lesions being either somatically induced by environmental agents or inherited through the germline. Familial adenomatous polyposis and hereditary non-polyposis colorectal cancer are the main types of inherited colorectal cancer. Sporadic colorectal cancer is though to involve several genes in a multistep pathway. Colorectal cancer occurs as a result of a series of genetic alterations in normal tissue that lead to disorganization in the molecular mechanisms that control growth. Most of the evidence incriminating diets as a major factor in the genesis of colorectal cancer. Case control studies and complex statistical analyses implicate both causative and protective dietary factors. The aim of screening is to detect neoplasia of the colon and rectum before it reaches an advanced stage, survival being directly related to the stage at presentation. The most sensitive evaluation of the whole colon is by colonoscopy. The way forward continues to rest with research into more sensitive occult fecal blood tests, more cost-effective endoscopic protocols and greater knowledge of the biological factors triggering dysplastic changes in large bowel mucosa.

Adenomatous Polyposis Coli↗